ADA: Switching to Liraglutide from Exenatide Improves Glycemic Control

The object of the study was to evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy.

When added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1c, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide.

All 389 patients completing 26 weeks entered the extension. Demographics were well matched between groups and similar to those previously reported. Overall, 376 of 389 patients (97%) completed the extension: 10 of 187 (5.3%) with exenatide→liraglutide and 3 of 202 (1.5%) continuing liraglutide withdrew. Withdrawals (n [%]) in the exenatide→liraglutide and liraglutide groups, respectively, were due to either adverse events (6 [3.2%] and 0), ineffective therapy (0 and 2 [1.0%]). Demographic and screening characteristics were similar between patients who withdrew during the extension and those who completed the extension, with the exception of mean duration of diabetes, which was longer for those withdrawing (12.2 years) than completers (7.9 years). 

Mean A1c further decreased from 7.2% at week 26 to 6.9% at week 40 (−0.32 ± 0.043%; P < 0.0001) after switching from exenatide to liraglutide, but remained similar with continued liraglutide (7.0 to 6.9%; −0.06 ± 0.041%, P = 0.1222) Additional patients reached A1c targets after switching from exenatide to liraglutide. 

Switching from exenatide to liraglutide further and significantly reduced A1c (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea.

This extension shows that patients can be simply and safely switched from twice-daily premeal exenatide to meal-independent once-daily liraglutide using weekly dose escalation from 0.6 to 1.2 to 1.8 mg. Conversion to liraglutide from exenatide was well tolerated and further improved glycemic control. Additional reductions in body weight and SBP occurred in both groups. Over 40 weeks, liraglutide reduced A1c by 1.3%.

The magnitude of these changes and differences between liraglutide and exenatide are consistent with results reported in phase 3 LEAD (liraglutide) and exenatide trials. The greater efficacy of liraglutide may be due to sustained levels achieved over 24 h by once-daily dosing compared with biphasic levels achieved during the 2.4-h half-life of exenatide after dosing within 1 h of breakfast and dinner.